Association of CETP Gene Variants with Atherogenic Dyslipidemia Among Thai Patients Treated with Statin

Abstract

Pornpen Srisawasdi,1 Punyanuch Rodcharoen,1 Somlak Vanavanan,1 Anchalee Chittamma,1 Chonlaphat Sukasem,2 Chalitpon Na nakorn,2 Charungthai Dejthevaporn,3 Martin H Kroll4 1Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 4Quest Diagnostics, Secaucus, NJ 07094, United States of AmericaCorrespondence: Pornpen Srisawasdi Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Rama VI Road, Ratchathewi, Bangkok 10400, ThailandTel [phone]Fax [phone]Email [email protected]: Patients treated with statins for dyslipidemia may still have a residual risk of atherosclerotic cardiovascular disease (ASCVD). To determine whether genetic variants in the cholesteryl ester transport protein (CETP), rs3764261 (C>A), rs708272 (G>A), and rs12149545 (G>A) affect ASCVD risk, we studied the association of these variants with dyslipidemia in statin-treated patients.Patients and Methods: We included 299 adult Thai patients treated with a statin (95 men and 204 women). Genotyping was performed by conducting a TaqMan real-time polymerase chain reaction-based analysis. We used logistic regression models adjusted for potential confounders of age, body mass index, blood pressure, insulin resistance, and statin dosage to analyze the association between CETP variants and atherogenic lipoprotein patterns.Results: CETP polymorphisms of rs3764261 and rs708272, but not rs12149545, were significantly associated with high-density lipoprotein cholesterol (HDL-C), apoA-I, triglycerides, very low-density lipoprotein (VLDL)-C, and large LDL (LDL1-C) levels as well as mean LDL particle size (all p < 0.020). However, no significant difference was observed in total cholesterol, LDL-C, or apoB levels by CETP variants. Regardless of sex, the combination of rs3764261 (CC genotype) and rs708272 (GG or GA genotypes) showed a stronger association with atherogenic dyslipidemia, including features of decreased HDL-C, elevated triglycerides, and LDL subclass pattern B (odds ratio [OR] =  2.99, 95% confidence interval [CI]: 1.78– 5.02) compared with the single variant rs3764261 (OR =  2.11, 95% CI: 1.27– 3.50) or rs708272 (OR =  2.12, 95% CI: 1.29– 3.49).Conclusion: The polymorphisms of CETP rs3764261 (CC genotype) and rs708272 (GG and GA genotypes) may have a higher susceptibility to atherogenic dyslipidemia. Testing for CETP rs3764261 and rs708272 may serve as a surrogate marker for lipid management in statin-treated patients, which may help individualize treatment for reducing the residual risk of ASCVD.Keywords: residual atherosclerotic risk, statin treatment, cholesteryl ester transport protein, genetic polymorphisms, genetic risk

Keywords

• residual atherosclerotic risk
• statin treatment
• cholesteryl ester transport protein
• genetic polymorphisms
• genetic risk.